What are the side effects of pain from intra-articular hyaluronic acid (HA) gel injections in the knee?

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Last updated: April 22, 2025View editorial policy

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From the Guidelines

Pain after gel knee injections is a common side effect that typically resolves within 24-48 hours, and can be managed with over-the-counter pain relievers, ice, elevation, and rest, as recommended by recent guidelines 1. To manage this discomfort, the following steps can be taken:

  • Apply ice to the knee for 15-20 minutes every 2-3 hours for the first day
  • Elevate your leg when sitting or lying down
  • Take over-the-counter pain relievers like acetaminophen (Tylenol) at a dose of 500-1000mg every 6 hours as needed, not exceeding 4000mg daily, as supported by the evidence 1
  • If able to take NSAIDs, ibuprofen (Advil, Motrin) at 400-600mg every 6-8 hours with food may help reduce both pain and inflammation, although it is essential to consider the potential risks and benefits, as noted in the guideline 1
  • Rest the knee for 24-48 hours, avoiding strenuous activities It is crucial to contact your healthcare provider if pain persists beyond 2-3 days, if you develop significant swelling, redness, warmth around the injection site, fever, or if the pain becomes severe, as these could be signs of a more serious complication 1. The side effects from gel knee injections, such as hyaluronic acid, occur because the needle insertion causes minor trauma to the tissues, and the injected gel can temporarily increase pressure within the joint space, stimulating pain receptors, as discussed in the context of intra-articular injections 1.

From the Research

Side Effects of Gel Knee Injections

  • The use of hyaluronic acid (HA) gel injections for knee pain has been studied, and while they can provide relief for osteoarthritis symptoms, there is limited information on the specific side effects of pain from these injections 2, 3.
  • Topical analgesics, such as those used in conjunction with HA, have been shown to have minimal adverse systemic effects compared to oral analgesics 4.
  • Intra-articular corticosteroid injections, which may be used in combination with HA gel injections, have relatively minor adverse effects, but oral and topical NSAIDs, including COX-2 inhibitors, are associated with increased risks in patients with certain comorbidities 5.
  • The most common indications for topical analgesics, including those potentially used with HA gel injections, are acute soft tissue injuries, neuropathic pain, and chronic joint-related conditions, such as osteoarthritis 4.

Potential Pain Side Effects

  • While there is limited direct evidence on the side effect of pain from gel knee injections, the use of HA and other topical analgesics has been shown to have anti-inflammatory and pain-relieving properties 2, 3.
  • The combination of HA with lidocaine and other co-agents may help reduce pain and improve skin tightness and elasticity 2.
  • However, the pharmaceutical management of osteoarthritis, including the use of gel knee injections, is a constantly evolving field, and clinicians should consider the latest evidence and recommendations to optimize treatment plans for patients 5.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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